Glucagon like-peptide-1-(7, 36)-amide (GLP-1) suppresses glucagon release and increases the early phase of insulin secretion. However, it is currently controversial as to whether GLP-1 alters insulin sensitivity. To address this question, we studied three subjects (to date) with type 2 diabetes mellitus on two occassions during which they were infused with either GLP-1 (1.2 pmol/Kg/Min) or normal saline. No postprandial insulin was infused. Volunteers also received a glucose infusion in a pattern mimicking that which appears in the systemic circulation after ingestion of 50 g of carbohydrate. Overnight euglycemia was achieved by a variable insulin infusion prior to the study. Endogenous hormone secretion was inhibited by somatostatin infusion, basal growth hormone, and glucagon were replaced so that their concentrations were identical on the two study days. A primed continuous infusion of 3-3H glucose was given to trace the glucose appearance and disappearance and endogenous glucose production. Basal plasma glucose concentrations were identical (p=) on the two study days as were peak plasma glucose concentration and glycemic excursion. Endogenous glucose production and rates of glucose disappearance were also identical on the two study days. We conclude that in the presence of identical insulin and glucagon concentrations, GLP-1 does not alter the ability of glucose to suppress glucose production and stimulate insulin-independent uptake. Future Plans: Given the negative results of 912-96 and 913-96, we conclude that GLP-1 has no effects on glucose effectiveness and insulin sensitivity when glucose is administered intravenously. However, we are in the process of preparing a protocol to examine the effect of GLP-1 on intestinal glucose uptake. This will be accomplished by using a nasoduodenal tube to deliver glucose indirectly into the portal circulation and subsequently observing the effect of GLP-1 on glycemic excursion.